. Nitric oxide and endothelin in oxygen-dependent regulation of vascular tone of human umbilical vein. Am J Physiol Heart Circ Physiol 285: H1730-H1737, 2003; 10.1152/ajpheart.00938.2002.-We investigated the possible contribution of nitric oxide (NO) and endothelin (ET) to oxygen-dependent regulation of human umbilical vein vascular tone by simultaneous registration of intracellular membrane potential and isometric tension of vessel strips with and without NO synthase inhibition [10 Ϫ4M N -nitro-L-arginine methyl ester (L-NAME)], ETA receptor blockade (10 Ϫ5 M BQ-123), or ETB receptor blockade (10 Ϫ7 M BQ-788) at PO2 values in the bath solution between 5 and 104 mmHg. Increasing PO2 above the physiological intrauterine range resulted in depolarization and an increase of isometric tension, whereas lowering PO2 resulted in hyperpolarization and a decrease in isometric tension. Removal of the endothelium reversed these effects. At PO2 values below 39 mmHg, intact preparations treated with either L-NAME, BQ-788, or BQ-123 were more depolarized than controls. In the case of treatment with L-NAME or BQ-123, this was accompanied by an increase in isometric tension. We conclude that it is NO that mediates the hypoxic hyperpolarization and vasodilatation of the human umbilical vein and that ET, via activation of ETB1 receptors on endothelial cells, contributes to this effect. membrane potential; endothelium; nitric oxide synthase inhibition; endothelin receptor antagonism BLOOD FLOW FROM THE PLACENTA to the fetus is determined by the difference between fetal aortic blood pressure and umbilical vein blood pressure, which in turn depends on umbilical vein vascular tone. The contribution of umbilical vein vascular tone to the regulation of umbilical blood flow had been regarded as negligible, because the umbilical vein was thought to operate at maximal vasodilatation already at resting conditions (6). However, a recent study (15) from our laboratory has revealed that the human umbilical vein is far from being a passive conduit, but is able to adjust its vascular tone in response to changes in local PO 2 . In particular, we found endothelium-dependent vasodilatation at hypoxia.Because the human umbilical vein is thought to lack autonomic innervation (4, 21), local mechanisms of regulation of vascular tone may be of particular relevance. Besides prostanoids, endothelial nitric oxide (NO) and endothelin (ET) are the most important locally released factors regulating vascular tone. There is a continuous basal release of NO from the vascular endothelium, and increased release of NO contributes to endothelium-dependent vasodilatation in response to various stimuli (16). We therefore asked whether NO contributes to oxygen-dependent regulation of human umbilical vein vascular tone and studied the effects of inhibition of NO synthesis by N -nitro-L-arginine methyl ester (L-NAME) on membrane potential and isometric tension of intact human umbilical vein preparations at different local PO 2 values.There is also evidence for a basal re...

Objective: To test the hypothesis that smooth muscle cells of the human umbilical vein have vasoconstricting endothelin B (ETB) receptors. Methods: In strip preparations of human umbilical veins isometric tension after exposure to the selective ETB receptor agonist sarafotoxin S6c (S6c) was compared to the tension before S6c exposure (set as 100%). Results: In intact preparations S6c induced vasoconstriction only at the highest concentration applied (10^–8M; 149.5 ± 12.5 vs. 100%, p < 0.05). In contrast, in endothelium-denuded preparations S6c induced vasoconstriction already at the lowest S6c concentration investigated (10^–11M; 111.7 ± 4.3 vs. 100%, p < 0.05). Conclusions: The vasoconstricting effect of S6c in endothelium-denuded human umbilical vein preparations points to smooth muscle cell ETB receptor activation.

No abstract

Background: Endothelin triggers vasoconstriction via activation of endothelin A (ETA) and endothelin B2 (ETB2) receptors on vascular smooth muscle cells and vasodilation by stimulating the release of nitric oxide via activation of endothelin B1 (ETB1) receptors on vascular endothelial cells.It is an open question if the human umbilical vein, besides ETA and ETB1 receptors, also has ETB2 receptors.Aim: To test if the human umbilical vein has ETB2 receptors. Methods: Strip preparations of human umbilical veins were superfused by Krebs solution. A pretension of 1 g was applied. Preparations were then exposed to the selective ETB receptor agonist sarafotoxin c (Sfc) (10 -11, 10 -10, 10 -9, or 10 -8 M). Only one concentration of Sfc was tested in each preparation. The isometric tension developed after the switch to Sfc was expressed as the percentage of that before Sfc exsposure. For each of the four Sfc concentrations used, we calculated the mean relative isometric tension developed by 7 intact and 5 endothelium-denuded preparations.Results: In intact preparations isometric tension did not change after exposure to Sfc (10 -11 to 10 -9 M). Only at the highest Sfc concentration (10 -8 M) isometric tension was higher than that developed in Krebs solution (149.5 Ϯ 12.5 vs. 100%, p Ͻ 0.05). In contrast, in endothelium-denuded preparations isometric tension increased after exposure to Sfc (10 -11 to 10 -8 M). Even at the lowest Sfc concentration (10 -11 M) isometric tension was significantly higher than that developed in Krebs solution (111.7 Ϯ 4.3 vs. 100%, p Ͻ 0.05).Conclusions: Vascular smooth muscle cells of the human umbilical vein have ETB2 receptors mediating contraction. In endothelium-denuded preparations the vasoconstricting effect of Sfc can be attributed to the activation of ETB2 receptors. In intact preparations this vasoconstricting effect appears to be counteracted in part by the vasodilating effect of the activation of ETB1 receptors on vascular endothelial cells. Background: Sick preterm infants have low levels of antithrombin (AT). It has been hypothesised that prophylactic administration of AT would prevent intraventricular haemorrhage (IVH). 248Method: We conducted a systematic review and meta-analysis of randomised, controlled trials that compared any dose of AT with placebo or no treatment, in preterm infants. This systematic review was conducted using the methods of The Cochrane Collaboration. Data were extracted from the published papers/abstracts. When appropriate we combined data from different trials into a meta-analysis using a fixed-effects model.Results: Three randomised trials, two published as full-text articles and one abstract, comprising 280 preterm infants, met our inclusion criteria. The mean gestational age, in the 2 full-text studies, was 28 weeks. The total dose of AT was comparable in these two studies, 500 U/Kg and 400 U/Kg, in divided doses over the first 48 hours of life. IVH was reported in all three trials; none of the individual trials found a significant statistical differe...